Schizophrenia Research 79 (2005) 231 – 238

www.elsevier.com/locate/schres

What does the PANSS mean?

Stefan Leucht a,b,*, John M. Kaneb, Werner Kisslinga, Johannes Hamanna,
Eva Etschelc, Rolf R. Engelc
a
Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Ismaningerstr. 22,
81675 München, Germany
b
Zucker Hillside Hospital, Albert Einstein College of Medicine 75-59 263rd Street, Glen Oaks, NY 11004, USA
c
Psychiatrische Klinik der Ludwig-Maximilian-Universität München, Nussbaumstrasse 7,
80336 München, Germany
Received 24 February 2005; received in revised form 31 March 2005; accepted 9 April 2005
Available online 27 June 2005

Abstract

Objective: Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of
schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to define treatment response (e.g. at least
20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of
Clinical Global Impressions (CGI).
Method: PANSS and CGI ratings at baseline (n = 4091), and after one, two, four and six weeks of treatment taken from a
pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with
exacerbations of schizophrenia were compared using equipercentile linking.
Results: Being considered bmildly illQ according to the CGI approximately corresponded to a PANSS total score of 58,
bmoderately illQ to a PANSS of 75, bmarkedly illQ to a PANSS of 95 and severely ill to a PANSS of 116. To be bminimally
improvedQ according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and
28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating bmuch improvedQ were 40%, 45%,
51% and 53%.
Conclusions: The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug
trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline

* Corresponding author. Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675
München, Germany. Tel.: +49 89 4140 4249; fax: +49 89 4140 4888.
E-mail addresses: Stefan.Leucht@lrz.tum.de (S. Leucht), psychiatry@lij.edu (J.M. Kane), W.Kissling@lrz.tum.de (W. Kissling),
J.Hamann@lrz.tum.de (J. Hamann), Eva.Etschel@med.uni-muenchen.de (E. Etschel), re@psy.med.uni-muenchen.de (R.R. Engel).

0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.schres.2005.04.008
232 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238
cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement
can be important, so that a 25% cut-off might be appropriate.
D 2005 Elsevier B.V. All rights reserved.
Keywords: Positive and Negative Syndrome Scale; Clinical Global Impressions Scale; Schizophrenia; Response; Clinical trials
1. Introduction
The Positive and Negative Syndrome Scale
(PANSS; Kay et al., 1987) was developed in order
to provide a well-defined instrument to specifically
assess both positive and negative symptoms of schizo-
phrenia as well as general psychopathology. Eighteen
items of the Brief Psychiatric Rating Scale (Overall
and Gorham, 1962) and twelve items of the Psychopa-
thology Rating Schedule (Singh and Kay, 1975) were
combined in one scale, and all items were given a
complete definition as well as detailed anchoring cri-
teria for all rating points. Strong psychometric proper-
ties in terms of reliability, validity and sensitivity have
been shown in a number of subsequent studies (for
summary see Kay et al., 2000). However, the clinical
implications of PANSS scores are not always clear. For
example, to our knowledge analyses have not been
carried out to estimate how ill a patient with a
PANSS total score of e.g. 60 or 100 is from a clinical
judgment point of view. Furthermore, in clinical studies
a reduction of at least 20%, 30%, 40% or 50% of the
initial PANSS score has been used as a cut-off to define
bresponseQ, but what these cut-offs mean from a global
bclinicalQ perspective is unclear. The Clinical Global
Impressions Scale (CGI; Guy, 1976) is, to a certain
extent more informative in this regard than the PANSS,
because it describes a patient’s overall clinical state as a
global impression made on the rater. It can also be
understood more intuitively by clinicians (Nierenberg
and DeCecco, 2002). The purpose of this study was
therefore to find corresponding points for simultaneous
PANSS and CGI ratings within a large sample of
patients with schizophrenia who were participating in
antipsychotic drug trials. Knowing what PANSS score
corresponds to a CGI-severity rating of e.g.
bmoderately illQ or bseverely illQ and what percentage
PANSS reduction from baseline corresponds to a CGI-
improvement rating of e.g. bminimally betterQ or
bmuch betterQ can increase our understanding of the
PANSS scores and the results of clinical trials. Such
information would be of interest to researchers, clin-
icians and sponsors.
2. Materials and methods
2.1. The database
We pooled original patient data from seven rando-
mised, double-blind trials (Beasley et al., 1996, 1997;
Breier et al., in press; Lieberman et al., 2003; Sèchter et
al., 2002; Tollefson et al., 1997; Tran et al., 1997; n at
baseline = 4091, 2671 male, 1420 female, age
37.1 F11.6 years, weight 75.9 F 17.2 kg, height
171 F10 cm) that compared olanzapine or amisulpride
with haloperidol, risperidone or placebo. Important
characteristics of the trials are presented in Table 1.
All studies were double blind and randomized. Each
trial examined patients with schizophrenia, schizoaf-
fective disorder or schizophreniform disorder accord-
ing to DSM-III-R (American Psychiatric Association,
1987) or DSM-IV (American Psychiatric Association,
1994) and all required minimum scores as eligibility
criterion to assure that the patients had florid symp-
toms. The mean PANSS total score at baseline in all
studies combined was 94 F 19 and the mean CGI-se-
verity scale was 4.8 F 0.9. The single items of the
PANSS were rated on a 7-point scale (1=absent,
2=minimal, 3=mild, 4=moderate, 5=moderate severe,
6=severe, and 7=extreme). Thus, the range of possible
PANSS total scores is from 30 to 210. The CGI-severity
scale (CGI-S; Guy, 1976) was also available for all
studies. The CGI-S assesses the clinician’s impression
of the patient’s current illness state. The rater is asked to
bconsider his total clinical experience with the given
populationQ. As with the PANSS, the time span con-
sidered is the week before the rating, and the following
scores can be given: 1=normal, not at all ill, 2=border-
line mentally ill, 3=mildly ill, 4=moderately ill,
5=markedly ill, 6=severely ill, and 7=among the most
extremely ill patients. The CGI-improvement scale
 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238 233

Table 1
Characteristics of the included studies
Study Antipsychotic n1 Weeks Mean age; gender Selected eligibility criteria
drugs used
Beasley et al., 1997 OLA, HAL 455 62 35.6 F 10.7; 165 F, 290 M Inpatients with acute exacerbations
of schizophrenia, DSM-III-R, BPRS
total score z42, CGI-S z 4
Tollefson et al., 1997 OLA, HAL 1996 62 38.6 F 11.4; 700 F, 1296 M In- and outpatients with schizophrenia,
schizophreniform- or schizoaffective
disorder, DSM-III-R, BPRS total score
z36
Beasley et al., 1996 OLA, PBO 154 62 37.7 F 9.2; 44 F, 110 M Inpatients with schizophrenia (residual
type excluded), DSM-III-R, BPRS total
score z42, CGI-S z 4
Tran et al., 1997 OLA, RIS 346 28 36.1 F10.7; 121 F, 225 M In- and outpatients with schizophrenia,
schizophreniform- or schizoaffective
disorder, DSM-IV, BPRS total score
z42
Lieberman et al., 2003 OLA, HAL 269 12 23.7 F 4.7; 48 F, 221 M In- and outpatients with a first episode
of schizophrenia, schizophreniform-
or schizoaffective disorder, DSM-IV,
at least two PANNS psychosis items
z4, CGI-S z 4
Breier et al., in press OLA, ZIP 561 28 39.2 F 12.0; 202 F, 359 M In- and outpatients with schizophrenia,
DSM-IV, BPRS total score z42, at
least one PANSS positive item z 4,
CGI-S z 4
Sèchter et al., 20023 AMI, RIS 310 52 38.5 F 10.8; 140 F, 170 M In- and outpatients with acute
exacerbations of schizophrenia,
DSM-IV, PANSS total score z60–120,
at least three PANSS positive items z4;
no predominant negative symptoms
1
Please note that in several studies the number of patients is a bit higher than in the original publications. The reason is that we included
patients who were ultimately not randomized, e.g. because they had responded during the placebo washout phase. 2 Durations of the acute
phases, there were long-term extensions. 3 The published report lasted only 6 months, but there was a 12 month extension; n=number of
patients, F=female, M=male, AMI=amisulpride, HAL=haloperidol, OLA=olanzapine, RIS=risperidone, CLO=clozapine, ZIP=ziprasidone,
CGI-S=Clinical Global Impression Severity Score, BPRS=Brief Psychiatric Rating Scale, DSM-III-R (-IV)=Diagnostic and Statistical Manual
of Mental Disorders, 3rd revision or 4th revision.

(CGI-I; Guy, 1976) assesses the patient’s improvement
or worsening since the start of the study using the
following scores: CGI-I: 1=very much improved,
2=much improved, 3=minimally improved, 4=no
change, 5=minimally worse, 6=much worse, 7=very
much worse). While all studies provided PANSS and
CGI-S ratings, only Beasley et al. (1997), Breier et al.
(in press), and Sèchter et al. (2002) provided CGI-I
ratings (n at baseline = 1432).
2.2. Statistical analysis
In the psychometric literature the search for
corresponding points on different, but correlated, mea-
surement devices is referred to as blinkingQ (Linn,
1993) or, in the case of completely parallel instruments,
as bequatingQ (Kolen and Brennan, 1995). Please note
already here that—although often used—a regression
analysis would not have been appropriate. Linear re-
gression treats one scale as the independent variable
measured without error and the other as the dependent
variable measured with error. This is conceptually
wrong because both variables are measured with ran-
dom error. For this study we used equipercentile link-
ing, a technique that identifies those scores on both
measures that have the same percentile rank. We ap-
plied the SAS program EQUIPERCENTILE (Price et
al., 2001), a realisation of the algorithms described by
234 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238

Kolen and Brennan (1995). In the first step, percentile
rank functions are calculated for both variables. Using
the percentile rank function of one variable and the
inverse percentile rank function of the other, one then
finds for every score of one variable a score on the other
variable that has the same percentile rank. The exact
formulas are described in chapter 2 of Kolen and
Brennan (1995). For each linking task we utilized all
patients with values which were valid on both mea-
sures. Although the duration of the studies ranged from
six to fifty-one weeks, not all studies provided data for
other time points, so that trial effects could have biased
the results. Thus only evaluations at baseline and at
weeks 1, 2, 4 and 6 were analyzed. A relatively large
number of patients (34.6%) dropped out between base-
line and week 6. In a sensitivity analysis we therefore
included only those patients who were still in the
studies at week 6 and who had a rating at each time
point. The results were very similar (see website for
additional material). An exception was the association
CGI-I (very) much worse versus percentage PANSS
change. Here a considerable variability was found,
probably in part due to the fact that only a small number
of patients who showed much deterioration of their
illness stayed in the studies. But CGI-I scores (very)
much worse are not commonly used as response criteria
anyway.
3. Results
Spearman correlation coefficients between CGI-
severity ratings and the PANSS total score were .56,
.62, .67, .72 and .73 for baseline, week 1, week 2,
week 4 and week 6 (N = 4065, 3906, 3706, 3356 and
2660, respectively). Spearman correlations between
CGI-improvement score and percentage improvement
of PANSS total baseline score were .70, .75, .74
and .71 for week 1, week 2, week 4 and week 6
(N = 1231, 1175, 1038 and 931, respectively).
3.1. Linking of the CGI-severity score and the PANSS
total score
Fig. 1 shows the result of the linking between the
CGI-severity scale and the PANSS total score at base-
line and at weeks 1, 2, 4 and 6. They suggest that being
considered bmildly illQ on the CGI (CGI-S = 3) corre-

CGI Severity Score

Extremely 7
ill

Severely 6
ill

Baseline n=4065
Markedly 5
ill Week 1 n=3906
Week 2 n=3706
Week 4 n=3356
Moderately Week 6 n=2660
ill 4

Mildly ill 3

Borderline
mentally ill 2

Normal 1
30 40 50 60 70 80 90 100 110 120 130 140 150
PANSS Total Score

Fig. 1. Linking of CGI-severity with the PANSS total score. The graph plots the corresponding (real) CGI score for every (integer) PANSS score.
For the reverse direction, the intersection of the lines indicates an integer CGI value with the graph providing the corresponding PANSS score.
 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238 235

sponded approximately to a PANSS total score of 61 at one, two, four and six are displayed in Fig. 2. Ratings
baseline; of 58 at weeks 1, 2, and 6; and of 57 at week of bminimally improvedQ (CGI-C = 3) at weeks one,
4. Being considered bmoderately illQ (CGI-S = 4) cor- two, four and six corresponded to a percentage
responded to a PANSS total score of 78 at baseline; of PANSS reduction of 19%, 23%, 26% and 28%,
76 at week 1; of 73 at week 4; and of 75 at weeks 2 and respectively. Ratings of bmuch improvedQ (CGI-
6. bMarkedly illQ (CGI-S = 5) corresponded to a C = 2) corresponded to percentage PANSS reductions
PANSS of 96 at baseline; of 95 at week 1; and of 93 of 40%, 45%, 51% and 53% at weeks one, two, four
at weeks 2, 4, 6. bSeverely illQ (CGI-S = 6) corre- and six, respectively. Ratings of bvery much
sponded to a PANSS of 118 at baseline; of 116 at improvedQ (CGI-C = 1) corresponded to percentage
weeks 1, 2 and 4; and of 115 at week 6. bAmong the PANSS reductions of 71%, 73%, 82% and 81%
most extremely ill patientsQ (CGI-S = 7) corresponded at weeks one, two, four and six. Thus there was a
to a PANSS of 147 at baseline and week 2, of 143 at consistent time effect indicating that a smaller
week 1, of 148 at week 4 and of 149 at week 6. Thus percentage PANSS change was necessary for a
the results were relatively consistent over the five time patient to be considered improved one week
points examined, although there was a slight tendency after the initiation of treatment than at later time
for the PANSS ratings to be somewhat more severe at points.
baseline and to become less severe in the course of the
treatment for a given CGI score. This effect, however,
was neither large nor consistent. 4. Discussion

3.2. Linking of the CGI-improvement score and the
percentage PANSS change from baseline
The linking functions between the CGI-I scale and
the percentage PANSS change from baseline at weeks
Very much worse
Much worse
The psychometric procedure of equipercentile
linking was used to compare the PANSS with Clin-
ical Global Impressions (CGI). The results can pro-
vide a better understanding of the PANSS and can
help clinicians to interpret the results of clinical
7
Week1 n=1231
Week2 n=1175
6 Week4 n=1038
Week6 n=931

Minimally worse 5
CGI Improvement

Unchanged 4

Minimally improved 3

Much improved 2

Very much improved

d
1
-100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100
PANSS Total: % Reduction from Baseline

Fig. 2. Linking of CGI-improvement with percentage PANSS reduction. The graph plots the corresponding (real) CGI score for every (integer)
PANSS score. For the reverse direction, the intersection of the lines indicates an integer CGI value with the graph providing the corresponding
PANSS score.
236 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238
trials. For example, the data indicate that trials in
which the average PANSS total score at baseline was
60 are unlikely to have examined a severely ill
population. Furthermore, frequently used cut-offs to
define bresponseQ in treatment trials—a 20% or 50%
reduction of the PANSS baseline scores—seem to
mean that on the average the patients were approx-
imately bminimally improvedQ and bmuch improvedQ
respectively according to the raters’ clinical impres-
sion. In treatment refractory patients even a small
improvement of symptoms such as a 20% or better a
25% PANSS reduction may be clinically important.
However, in acutely ill, non-refractory patients a
50% criterion (i.e. clinically much improved) seems
to be a more appropriate reflection of clinically
meaningful improvement, because such patients usu-
ally respond well to antipsychotic drugs (Cole,
1964). In contrast to our findings, recent antipsychot-
ic drug trials in patients with acute exacerbations
often used a 20% criterion to distinguish between
responders and non-responders. This development
may be explained in part by the use of the 20%
cut-off in a landmark study on clozapine (Kane et
al., 1988). Ironically, while this study did indeed
examine refractory patients, the 20% cut-off was
subsequently widely applied in studies of non-refrac-
tory subjects. However, it has been argued that many
patients who are nowadays included in antipsychotic
drug trials have had suboptimal response to previous
treatment. Concrete information is usually not docu-
mented, but if this were the case the use of lower
thresholds would be understandable.
A strength of our analysis is the large number of
patients included, which makes the results relatively
robust. However there are also a number of limita-
tions. Since we used drug trial data, both floor and
ceiling effects need to be discussed. Floor effects in
the CGI-severity/PANSS total score comparison did
not bias the results because even though the studies
demanded a minimum of symptoms at baseline, this
was not the case at six weeks, yet the association was
virtually identical. In the CGI-improvement/percent-
age PANSS reduction comparison it was necessary for
the patients to have a minimum of symptoms at
baseline to make the analysis possible. Ceiling effects
cannot be ruled out because patients must have a
minimum level of understanding and cooperativeness
in order to be able to sign the informed consent before
the trial. The results are therefore representative only
of antipsychotic drug trial populations and not of all
patients in routine clinical practice.
A further methodological problem is that despite
the widespread use of the CGI in drug trials, its
psychometric characteristics are not well defined, be-
cause the latter have been examined in only a few
studies (Leon et al., 1993; Khan et al., 2002, 2004;
Beneke and Rasmus, 1992) so that the CGI is certain-
ly not an ideal measure for bevaluatingQ the PANSS.
An assumption is that the PANSS and the CGI mea-
sure similar conditions. The PANSS examines a num-
ber of schizophrenic symptoms in addition to a
number of general psychopathology measures while
the CGI assesses the patient’s bcurrent illness state
according to the rater’s total clinical experience with
the given populationQ (Guy, 1976). It is likely that
physicians rating the CGI base their judgement mainly
on the symptoms that are also measured in the
PANSS, especially if the CGI is filled in simulta-
neously with the PANSS. But the instruments do of
course also differ, as is reflected by the correlation
coefficients for the CGI-severity versus PANSS total
score comparison between .56 and .73. One explana-
tion for the correlation coefficient at baseline being
the lowest is that the variability of both PANSS and
CGI ratings was reduced by the symptom thresholds
required to be eligible for the studies. Given these
differences of the PANSS and the CGI, linking in our
application is no more than a kind of anchoring that
helps in understanding the clinical implications of a
given scale score.
There was a time effect in the percentage PANSS
reduction results, suggesting that a somewhat smaller
bobjectiveQ percentage change as measured by the
PANSS was necessary for patients to be considered
improved according to the CGI-I one week after the
initiation of treatment than at later weeks. This result
probably reflects physicians’ expectations. After one
week of treatment a relatively small objective change
maybe regarded as a considerable improvement
according to a rater’s CGI assessment, while at six
weeks the expectation has risen and a more objective
reduction of symptoms is needed for the same CGI-
improvement score. Furthermore, a problem of the
CGI-improvement score is that the rating must com-
pare a patient’s current state with the baseline state.
The longer the study lasts, the harder it is to remem-
 S. Leucht et al. / Schizophrenia Research 79 (2005) 231–238
ber a patient’s baseline condition exactly. Neverthe-
less the time effect of the CGI-I/percent PANSS
reduction relationship does not call into question
our main conclusion that the 20% PANSS reduction
threshold does not reflect much improvement accord-
ing to a clinical impression. A replication with a
recently developed, better anchored version of the
CGI for schizophrenia with verified validity and re-
liability (Haro et al., 2003) would be useful. Such
data could also show that a more objective measure
of clinical psychopathology might be obtained by
raters who were blind to which week of participation
the patient is in (thereby eliminating expectation
bias).
The results might not be the same when different
patient populations are analyzed. While all studies in
our database used certain minimum scores as eligibil-
ity criteria to assure that the patients had florid symp-
toms and three studies also required a minimum of
psychotic symptoms (Breier et al., in press; Lieber-
man et al., 2003; Sèchter et al., 2002), the exact
criteria differed. This is an advantage, not a limitation,
of our database because although the inclusion criteria
in such studies are similar, the exact definitions are
more or less arbitrarily chosen so that assembling a
number of such studies increased generalizability.
However it is difficult to characterize the database
using a single term. It could be said that all studies
tried to include btypicalQ patients (with a requirement
of a minimum of psychotic symptoms in three of them
(Breier et al., in press; Lieberman et al., 2003; Sèchter
et al., 2002)), because their aim was to obtain results
that can be generalized to routine care. But defining
the term btypicalQ or baverageQ in this context is
difficult at best. The studies did not explicitly select
patients with more specific characteristics such as
predominant negative symptoms or previous treat-
ment resistance, and none of the studies were intended
to include patients who were in relative remission. We
included one study with a first episode of schizophre-
nia (n = 269, i.e. only 6.6% of the PANSS vs. CGI-S
analysis, the CGI-I was not used in this study any-
way), but a sensitivity analysis excluding this study
did not change the results to any important degree.
Furthermore, the other studies contained a number of
first episode patients as well. In populations with
specific symptoms, however, the results of our linking
analysis might be very different. For example, some
237
clinicians might consider patients suffering only from
negative symptoms to be severely ill according to the
CGI, but they would have relatively low PANSS total
scores due to a lack of positive symptoms. Similarly, a
50% PANSS total score reduction may have a differ-
ent clinical meaning in such a population. We there-
fore hasten to emphasize that our results relate only to
patients with schizophrenia and acute symptoms sim-
ilar to those included in our database. Future studies
should examine other patient populations (e.g.
patients with residual schizophrenia and primary neg-
ative symptoms), use anchored versions of the CGI
and specifically trained raters.
Acknowledgements
We are indebted to EliLilly and Sanofi-Synthélabo
for the possibility of analyzing individual patient data
from their databases. This study was supported by a
grant for the Zucker Hillside Hospital Intervention
Research Center for Schizophrenia (MH-60575).
Appendix A. Supplementary data
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/
j.schres.2005.04.008.
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